Sunscreen Compositions Comprising Uniform, Rigid, Spherical, Nanoporous Calcium Phosphate Particles and Methods of Making and Using the Same

ABSTRACT

Aspects of the invention include sunscreen formulations that include uniform, rigid, spherical nanoporous calcium phosphate particles. Also provided are methods of making the sunscreen formulations. The sunscreen formulations find use in sunblocking applications.

CROSS-REFERENCE TO RELATED APPLICATIONS

Pursuant to 35 U.S.C. §119 (e), this application claims priority to thefiling date of U.S. Provisional Patent Application Ser. No. 61/259,935filed Nov. 10, 2009; the disclosure of which application is hereinincorporated by reference.

INTRODUCTION

It is well recognized that solar ultraviolet (UV) radiation poses aserious threat to human skin, which may range from the short term hazardlike erythema, i.e., sunburn, to long term hazards like skin cancerand/or premature aging of the skin. UV radiation having a wavelength of290 nm to 320 nm, generally referred to as UVB radiation, is known tocause erythema. In addition, numerous studies point to exposure ofunprotected skin to UV radiation having a wavelength of from 320 nm to400 nm, generally referred to as UVA radiation, as being the primarycause of skin cancer. It is important therefore, that skin is protectedfrom both UVA and UVB radiations to avoid the long and short termdeleterious effects of solar radiation.

The sun protection factor (SPF) rating system has been developed to helpconsumers select the appropriate sun protection product for any givenoutdoor activity involving exposure to the sun. The SPF ratingcorresponds to a multiplying factor by which the duration of protectionby a properly applied sunscreen exceeds the exposure time that causesunprotected skin to darken. Thus, with proper application of an SPF 8product, a person should be able to remain in the sun without skindarkening for eight times the usual unprotected duration.

In recent years, due to the increased public awareness of UV radiationhazards, the use of sun protection products has grown considerably, withconsumers preferring products that have high SPF ratings and offerprotection over the entire range of UV radiation, i.e., from 290 nm to400 nm. These products typically contain certain UV-absorbers that areapproved for use in sunscreen compositions by regulatory agencies (forexample, US Food and Drug Administration (FDA) in the USA and COLIPA inthe European Union). These approved UV-absorbers are either organiccompounds, referred to in the art as organic UV-absorbers or sunscreens,or inorganic compounds, referred to in the art as inorganic UV-absorbersor sunscreens. At present, approved inorganic UV-absorbers are inorganicoxides such as titanium dioxide (TiO₂) and zinc oxide (ZnO). Among theseinorganic oxide sunscreens, ZnO is capable of absorbing substantialamounts of UVA-radiation, and hence is often used as a UVA-sunscreen.

SUMMARY

Aspects of the invention include sunscreen formulations that includeuniform, rigid, spherical nanoporous calcium phosphate particles. Alsoprovided are methods of making the sunscreen formulations. The sunscreenformulations find use in sunblocking applications.

DETAILED DESCRIPTION

Aspects of the invention include sunscreen formulations that includeuniform, rigid, spherical nanoporous calcium phosphate particles. Alsoprovided are methods of making the sunscreen formulations. The sunscreenformulations find use in sunblocking applications.

Before the present invention is further described, it is to beunderstood that this invention is not limited to particular embodimentsdescribed, as such may vary. It is also to be understood that theterminology used herein is for the purpose of describing particularembodiments only, and is not intended to be limiting, since the scope ofthe present invention will be limited only by the appended claims.

Where a range of values is provided, it is understood that eachintervening value, to the tenth of the unit of the lower limit unlessthe context clearly dictates otherwise, between the upper and lowerlimit of that range and any other stated or intervening value in thatstated range, is encompassed within the invention. The upper and lowerlimits of these smaller ranges may independently be included in thesmaller ranges and are also encompassed within the invention, subject toany specifically excluded limit in the stated range. Where the statedrange includes one or both of the limits, ranges excluding either orboth of those included limits are also included in the invention.

Certain ranges are presented herein with numerical values being precededby the term “about.” The term “about” is used herein to provide literalsupport for the exact number that it precedes, as well as a number thatis near to or approximately the number that the term precedes. Indetermining whether a number is near to or approximately a specificallyrecited number, the near or approximating unrecited number may be anumber which, in the context in which it is presented, provides thesubstantial equivalent of the specifically recited number.

Methods recited herein may be carried out in any order of the recitedevents which is logically possible, as well as the recited order ofevents.

Unless defined otherwise, all technical and scientific terms used hereinhave the same meaning as commonly understood by one of ordinary skill inthe art to which this invention belongs. Although any methods andmaterials similar or equivalent to those described herein can also beused in the practice or testing of the present invention, the preferredmethods and materials are now described.

All publications mentioned herein are incorporated herein by referenceto disclose and describe the methods and/or materials in connection withwhich the publications are cited.

It must be noted that as used herein and in the appended claims, thesingular forms “a”, “an”, and “the” include plural referents unless thecontext clearly dictates otherwise. It is further noted that the claimsmay be drafted to exclude any optional element. As such, this statementis intended to serve as antecedent basis for use of such exclusiveterminology as “solely,” “only” and the like in connection with therecitation of claim elements, or use of a “negative” limitation.

The publications discussed herein are provided solely for theirdisclosure prior to the filing date of the present application. Nothingherein is to be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.Further, the dates of publication provided may be different from theactual publication dates which may need to be independently confirmed.

Sunscreen Formulations Comprising Uniform, Rigid, Spherical, NanoporousCalcium Phosphate Particles

Aspects of the invention include sunscreen compositions. While the SPFvalue of sunscreen compositions of the invention may vary, in someinstances the compositions have an SPF value of 4 or more, e.g., 8 ormore, 15 or more, 20 or more, 30 or more, 40 or more, 50 or more, 60 ormore, including 70 or more. The compositions may have a UV-A protectionvalue of 1 or more, such as 2 or more, e.g., 2.25 or more, etc., such as4 or more, e.g., 8 or more, 15 or more, 20 or more, 30 or more, 40 ormore, 50 or more, 60 or more, including 70 or more. SPF and UV-Aprotection values may be determined using any convenient protocol, suchas the protocols reported in the Experimental Section, below.

As summarized above, aspects of the invention include sunscreenformulations. Sunscreen formulations of the invention include uniform,rigid, spherical, nanoporous calcium phosphate particles in a sunscreendelivery vehicle, where the sunscreen delivery vehicle may or may notinclude additional sunscreens, e.g., organic or inorganic sunscreens.Each of these components is now described separately in greater detail.

Uniform, Rigid, Spherical, Nanoporous Calcium Phosphate Particles

The calcium phosphate particles of the sunscreen formulations describedherein are uniform, rigid, spherical, nanoporous calcium phosphateparticles. By “uniform” is meant that the shape of the particles doesnot vary substantially, such that the particles have substantially thesame spherical shape. By “rigid” is meant that the particles are hard,such that they are not pliant. The term “spherical” is employed in itsconventional sense to mean a round body whose surface is at all pointssubstantially equidistant from the center. Of interest are calciumphosphate particles in which the median diameter is 100 μm or less, suchas 75 μm or less, including 50 μm or less, e.g., 25 μm or less, such as20 μm or less, such as 10 μm or less, including 5 μm or less, where insome instances the medium diameter is 4 μm or less, such as 3 μm orless, including 2 μm or less, including 1 μm or less, including 0.1 μmor less. In a given calcium phosphate particulate composition, adistribution of diameters may be present, where in some instances themajority (such as 60% or more, 75% or more, 90% or more, 95% or more) ofthe particles have diameters that range from 0.01 to 20 μm, such as from0.1 to 10 μm, and including from 0.1 to 2 μm. In some instances, theproportion of the particles that have an average particle diameter of 2μm or less is 50% or more by number, such as 70% or more by number,including 90% or more by number. In some instances, the compositionsincludes two more distinct populations of particles that differ fromeach other in terms if diameter, e.g., where the magnitude of thedifference may be 10% or more, such as 20% or more. The number ofdistinct population sizes may vary, and in some instances may be 2 ormore, such as 3 or more, 4 or more, 5 or more, 6 or more, etc. In suchembodiments, each distinct population may be present in varying amountswith respect to the total amount of calcium phosphate particles, e.g.,where each distinct population is present in an amount ranging from 0.5to 99.5% by weight, such as 1 to 75% by weight, including 1 to 50% byweight of the total weight of the calcium phosphate particles.

The particles are nanoporous. By “nanoporous” is meant that theparticles have a porosity of 30% or more, such as 40% or more, including50% or more, where the porosity may range from 30% to 85%, such as from40% to 70%, including from 45% to 55%, as determined using a mercuryintrusion porosimeter porosity determination protocol as described inASTM D 4284-88 “Standard Test Method for Determining Pore VolumeDistribution of Catalysts by Mercury Intrusion Porosimetry”. Porosity isalso described by “pore volume (ml/g)” and in such instances many rangefrom 0.1 ml/g to 2.0 ml/g. In some cases, the particles have a porositysuch that their internal surface area ranges from 10 m²/g to 150 m²/g,such as from 20 m²/g to 100 m²/g, including 30 m²/g to 80 m²/g, asdetermined using a BET gas adsorption surface area determinationprotocol as described in ASTM D3663-03 Standard Test Method for SurfaceArea of Catalysts and Catalyst Carriers. The pore diameter may vary,ranging in certain instances from 2 to 100 nm, such as 5 to 80 nm,including 10 to 60 nm. In addition, the particles may have a tappingdensity ranging from 0.2 g/cm³ to 0.5 g/cm³, such as from 0.25 g/cm³ to0.45 g/cm³, including from 0.3 g/cm³ to 0.4 g/cm³. The tap density canbe measured by using standard ASTM WK13023—New Determination of TapDensity of Metallic Powders by a Constant Volume Measuring Method.

The particles are, in some instances, not activated with trace elements,such that they do not include amounts of trace elements such as Zn, Mn,or Mg. In some instances, the particles do no include at least partialsubstitution of an organic anion, e.g., lactate, for the hydroxideanion. In some instances, the particles are not apalight, i.e., thechemical formula of the particles is not (Zn, Mn,Mg)Ca₅(PO₄)₃(OH)(Lactate). The particles are, in some instances,chemically pure. By chemically pure is meant that the particles are madeup of substantially one type of calcium phosphate mineral. In someinstances, the calcium phosphate particles are described by themolecular formula Ca₁₀(PO₄)₆(OH)₂.

In some instances, the particles are ceramic particles. By ceramic ismeant that the particles are produced using a method which includes astep of subjecting the particles to high temperature conditions, wheresuch conditions are illustrated below. High temperatures may range from200 to 1000° C., such as 300 to 900° C. and including 300 to 800° C. Insome embodiments, the particles have a compression rupture strengthranging from 20 to 200 MPa, such as from 50 to 150 MPa, and including 75to 90 MPa, as determined using a SHIMADZU MCT-W500 micro-compressiontesting machine particle strength determination protocol with a particlesintered at temperature of 400° C. to 900° C., as described in EuropeanPatent EP1840661.

In some embodiments, the particles are biodegradable, by which is meantthat the particles degrade in some manner, e.g., dissolve, over timeunder physiological conditions. As the particles of these embodimentsare biodegradable under physiological conditions, they at least begin todissolve at a detectable rate under conditions of pH of 5 or less, suchas 4.5 or less, including 4.3 or less. As such, the particles exhibitsolubility under acidic environments of pH 5 or less, such as uponapplication to the skin.

The calcium phosphate particles are non-toxic, e.g., as determined viaUS-FDA 21 CFR Part 58, non-mutagenic, e.g., as determined byMutagenicity Ames Test, and non-irritating, e.g., as determined via SkinSensitization RIPT (Human).

While the uniform, rigid, spherical, nanoporous calcium phosphateparticles of the sunscreen compositions may vary in a variety ofdifferent parameters, including as reviewed above, in some embodimentsthe particles employed in the sunscreen compositions are chemically pureparticles that have a mean diameter of 2 μm.

The uniform, rigid, spherical, nanoporous calcium phosphate particles ofthe sunscreen compositions of the invention may be prepared using anyconvenient protocol. Examples of fabrication protocols of interestinclude, but are not limited to, those described in U.S. Pat. Nos.4,781,904; 5,039,408; 5,082,566; and 5,158,756; the disclosures of whichare herein incorporated by reference. In one protocol of interest, theparticles are manufactured by spray drying a slurry that includes nanocalcium phosphate (e.g., hydroxyapatite) crystals (which may range from2 nm to 100 nm size range) to produce uniform spherical nanoporouscalcium phosphate particles. The resultant particles are then sinteredfor a period of time sufficient to provide mechanically and chemicallystable rigid spheres. In this step, the sintering temperatures may rangefrom 200° C. to 1000° C., such as 300° C. to 900° C. and including 300°C. to 800° C. for a period of time ranging from 1 hour to 10 hours, suchas 2 hours to 8 hours and including 3 hours to 6 hours. Additionaldetails regarding this method of manufacturing the uniform, rigid,spherical, nanoporous calcium phosphate particles are provided in U.S.Provisional Application Ser. No. 61/108,805, the disclosure of which isherein incorporated by reference.

Where desired, initially porous particles, e.g., as described above, maybe rendered non-porous prior to combination with the sunscreen deliveryvehicle in preparing the sunscreen compositions. Accordingly, in someinstances the calcium phosphate particles present in the sunscreencompositions are non-porous. In these embodiments, initially porousparticles may be combined with a suitable filler, e.g., an inert filler,so that the porosity of the pores is reduced by a desired amount. Insuch applications, loading protocols described in copending applicationSer. No. 12/565,687 (the disclosure of which is herein incorporated byreference), may be employed.

In addition, as further described below, the particles may also beloaded with one or more components of the sunscreen composition, e.g.,organic or inorganic sunscreen blocking agents, antioxidants, etc.

Sunscreen Delivery Vehicle

Sunscreen compositions of the invention include a suitable amount of theabove described particles present in a sunscreen delivery vehicle (i.e.,topical delivery vehicle) that is configured for application to atopical site of a living subject, such as a human. As such, sunscreencompositions of the invention are compositions that are formulated forapplication to a keratinized skin surface of a mammalian subject, suchas a human subject. By keratinized skin surface is meant a skin locationof a subject, i.e., a location of the external covering or integument ofan animal body. Because the topical compositions of the invention areformulated for delivery to topical location, they are formulated so asto be physiologically compatible with the topical location for whichthey are formulated. Accordingly, when contacted with the targetkeratinized skin surface for which they are formulated, the topicalcompositions do not cause substantial, if any, physiological responses(such as inflammation or irritation) that would render the use of thetopical compositions unsuitable for topical application.

As indicated above, the sunscreen compositions include an amount ofuniform, rigid, spherical nanoporous calcium phosphate particles, e.g.,as described above. In a given sunscreen composition, a distribution ofdiameters for the particles thereof may be present, where in someinstances the majority (such as 60% or more, 75% or more, 90% or more,95% or more) of the particles have diameters that range from 0.01 to 20μm, such as 0.05 to 15 μm such as from 0.1 to 10 μm, and including from0.1 to 2 μm. In some instances, the proportion of the particles thathave an average particle diameter of 2 μm or less is 50% or more bynumber, such as 70% or more by number, including 90% or more by number.In some instances, formulations are manufactured to include two or more,including 3 or more, 4 or more, 5 or more, etc., discrete particle sizepopulations, where each particle size population has a different averageparticle size. For example, a composition may include a first particlesize population having an average particle size ranging from 0.1 to 2 μmand a second particle size population having an average particle sizeranging from 2 to 20 μm. Where two or more different particle sizepopulations are present, the difference in average particle size betweenany two particle size populations may vary, and in certain embodimentsis 1 μm or greater, such as 2 μm or greater, including 3 μm or greater,5 μm or greater, and 10 μm or greater.

The total amount of a particles that is present in a given sunscreencomposition and therefore combined with a sunscreen delivery vehicle mayvary. In some instances, the total amount of calcium phosphate particlespresent in the composition is sufficient to increase the SPF factor ofthe composition as compared to a control (i.e., the same formulationlacking the calcium phosphate particles) by a magnitude of 1 or more,such as 2 or more, e.g., 3 or more, 4 or more, 5 or more, 6 or more, 7or more, 8 or more, 9 or more, 10 or more, where in some instances themagnitude increase in SPF factor ranges from 0.5 to 5, such as 1 to 4,e.g., 2 to 3. In some instances, the total amount of calcium phosphateparticles present in the composition is sufficient to increase the UV-Aprotection value of the composition as compared to a control (i.e., thesame formulation lacking the calcium phosphate particles) by a magnitudeof 0.1 or more, such as 0.2 or more, e.g., 0.3 or more, 0.4 or more, 0.5or more, 0.6 or more, 0.7 or more, 0.8 or more, 0.9 or more, 1.0 ormore. In some embodiments, the amount of particles present in thedelivery vehicle ranges from 0.01 to 200 mg/g, such as 0.1 to 100 mg/gand including 1 to 50 mg/g active agent loaded particles per gram ofdelivery vehicle. In certain embodiments the particles are present incompositions in an amount ranging from about 0.001 to about 80% byweight, such as from about 0.01 to about 70% by weight, and includingfrom about 0.05 to about 60% by weight, e.g., 0.1 to 10% by weight, suchas 0.1 to 5% by weight, including 1% by weight.

As indicated above, the sunscreen compositions of the invention furtherinclude a sunscreen delivery vehicle. The sunscreen delivery vehicle(i.e., topical delivery component) refers to that portion of thesunscreen composition that is not the calcium phosphate particles, wherethis portion of the sunscreen composition may include a number ofdifferent and varying components, as reviewed below. Sunscreen deliveryvehicles of interest include vehicles formulated for application to atopical region or surface of a subject, such as a keratinized skinsurface. The subject compositions may be formulated as stable solutionsor suspensions of the components, e.g., in an aqueous solvent. Wheredesired, the components may be combined with one or more carriermaterials to form a solution, suspension, gel, lotion, cream, ointment,aerosol spray or the like, as desired. In some instances, the sunscreendelivery vehicle is an oil-in-water or water-in-oil emulsioncomposition.

Sunscreen delivery vehicles of interest include, optionally, one or moreadditional sunscreens and a carrier.

Additional Sunscreens

In some instances, the sunscreen composition of the invention mayinclude an amount of an additional sunscreen component, e.g., UVabsorber or UV scatterer, which may be inorganic or organic. Theadditional sunscreen component (such as UV absorber) may absorb and/orphysically block UV-B radiation, e.g., UV-B and/or both UV-A radiation.In some instances, one or more additional sunscreen components may bepresent in type and amount that provides for more UV-B screening thanUV-A screening, e.g., in compositions configured or formulated toprovide for the occurrence of a “natural” tan. In some instances, thesunscreen compositions of the present invention will be effectiveagainst both UV-A and UV-B and have either strong UV-A/UV-B sunblockactives or the presence of an additional UV-A sunblock active, e.g., toprovide a balanced UV-A/UV-B blocking composition. Of interest areinorganic actives that work by reflecting the UV light and organicactives that work, predominately, by absorbing UV energy. The amount ofthe sunblock active to be incorporated into the sunscreen formulations,when present, may vary.

Organic sunscreen components of interest include, but are not limitedto, avobenzone, butyl methoxydibenzoylmethane, cinoxate, benzophenone-8,dioxybenzone, homosalate, octylsalate, menthyl anthranilate,octocrylene, ethyhexyl methoxycinnamate, octyl methoxycinnamate, octylsalicylate, oxybenzone, padimate O, ethylhexyl salicylate,benzophenone-3, p-aminobenzoic acid (PABA), ethylhexyl dimethyl PABA,glyceryl PABA, phenylbenzimidazole sulfonic acid, sulfisobezone,trolamine salicylate, 4-methylbenzylidene camphor, bisoctrizole,bemotrizinol, ecamsule, drometrizole trisiloxane, disodium phenyldibenzimidazole tetrasulfonate, diethylamine hydroxybenzoyl hexylbezoate, octyl triazone, hexyl benzoate, benzophenone-4, ethyhexyltriazone, diethylhexyl butamido triazone, bisimidazylate,polysilicone-15, 2-ethylhexyl 2-cyano-3,3-diphenyl-2-propenoate(octrocrylene), etc.

Inorganic sunscreens of interest include, but are not limited to,titanium oxide, e.g., microfine surface treated titanium dioxide, andzinc oxide, e.g., microfine untreated and surface treated zinc oxide.The titanium dioxide in the sunscreen compositions may have a meanprimary particle size of between 5 and 150 nm, preferably between 10 and100 nm. Titanium oxide may have an anatase, rutile, or amorphousstructure. The zinc oxide in the sunscreen compositions preferably has amean primary particle size of between 5 nm and 150 nm, preferablybetween 10 nm and 100 nm.

In some instances, the sunscreen compositions of the present inventionwill comprise a combination of such sunblock actives. As such, in someinstances the sunscreen composition include, in addition to the calciumphosphate particles described above, combinations of both inorganic andorganic sunscreen components. In some instances, the sunscreencomponents are chosen from the following list of agents: p-aminobenzoicacid (PABA); padimate O (OD-PABA, octyldimethyl-PABA, σ-PABA);phenylbenzimidazole sulfonic acid (Ensulizole, Eusolex 232, PBSA, ParsolH); cinoxate (2-Ethoxyethyl p-methoxycinnamate), dioxybenzone(Benzophenone-8), oxybenzone (Benzophenone-3, Eusolex 4360, Escalol567), homosalate (Homomethyl salicylate, HMS), menthyl anthranilate(Meradimate), octocrylene (Eusolex OCR, 2-cyano-3,3diphenyl acrylicacid, 2-ethylhexylester), octylmethoxycinnamate (Octinoxate, EMC, OMC,Ethylmethoxycinnamate, Escalol 557, 2-ethylhexyl-paramethoxycinnamate,Parsol MCX), octyl salicylate (Octisalate, 2-Ethylhexyl salicylate,Escalol 587), sulisobenzone (2-Hydroxy-4-Methoxybenzophenone-5-sulfonicacid, 3-benzoyl-4-hydroxy-6-methoxybenzenesulfonic acid, Benzophenone-4,Escalol 577), trolamine salicylate (Triethanolamine salicylate),avobenzone (1-(4-methoxyphenyl)-3-(4-tert-butylphenyl)propane-1,3-dione,Butyl methoxy dibenzoylmethane, BMDBM, Parsol 1789, Eusolex 9020),ecamsule (Mexoryl SX, Terephthalylidene Dicamphor Sulfonic Acid),titanium dioxide, zinc oxide, 4-methylbenzylidene camphor (Enzacamene,Parsol 5000, Eusolex 6300, MBC), tinosorb M (Bisoctrizole, MethyleneBis-Benzotriazolyl Tetramethylbutylphenol, MBBT), tinosorb S(Bis-ethylhexyloxyphenol methoxyphenol triazine, Bemotrizinol, BEMT,anisotriazine), neo heliopan AP (Bisdisulizole Disodium, Disodium phenyldibenzimidazole tetrasulfonate, bisimidazylate, DPDT), mexoryl XL(Drometrizole Trisiloxane), benzophenone-9 (Uvinul DS 49, CAS 3121-60-6,Sodium Dihydroxy Dimethoxy Disulfobenzophenone), uvinul T 150 (Octyltriazone, ethylhexyl triazone, EHT), uvinul A plus (DiethylaminoHydroxybenzoyl Hexyl Benzoate), uvasorb HEB (Iscotrizinol, Diethylhexylbutamido triazone, DBT), parsol SLX (Dimethico-diethylbenzalmalonate,Polysilicone-15), isopentenyl-4-methoxycinnamate (Isoamylp-Methoxycinnamate, IMC, Neo Heliopan E1000, Amiloxate)

The amounts of sunscreens which are employed in any given compositionwill vary, e.g., depending upon the sunscreen chosen and the desired SunProtection Factor (SPF) to be achieved.

Carrier

The sunscreen delivery vehicles include a carrier, which is thatcomponent of the vehicle which is not the inorganic or organic sunscreencomponents, e.g., as described above (it is noted that in thoseinstances where the vehicle does not include an additional sunscreencomponent, the carrier and the vehicle are the same, such that thecarrier is not a component of the vehicle but is the entire vehicle).The carrier is that material or combination of materials that is used toessentially carry or deliver the calcium phosphate particles, sunblockactive(s) when present) to the skin. The specific carrier material thatis present in a given sunscreen composition will depend upon the desireddelivery method for the composition, e.g., spray one, rub on, etc. Forexample, as mentioned earlier, the sunscreen compositions may be in theform of lotions, creams, gels, foams, emulsions, dispersions, sprays,liposomes, coacervates, etc. Each composition may include any convenienttopical excipient and like agents desirable for achieving the particularform. Of interest are carriers that include an amount of water, e.g.,30% by weight or more, such as 40% by weight or more. Excipients ofinterest may include, e.g., mineral oils and emulsifying agents. In itsmost simplest of embodiments, the carrier may be water, alcohol orwater/alcohol combinations, or other solvent(s) or solvent systems inwhich the aforementioned actives may be, e.g., soluble, dispersed,emulsified, etc. In some instances, sunscreen compositions of interestwill include excipients and the like that create a substantially stable,homogenous sunscreen composition and/or provide body and viscosity tothe sunscreen composition so that the actives do not merely run off theskin once applied. In some instances, the carrier will comprise from 30to 99% by weight of the sunscreen composition. Any known carrier or basecomposition may be present in the sunscreen compositions of theinvention. Suitable carriers and carrier compositions of interestinclude, but are not limited to: those described in U.S. Pat. Nos.7,186,404; 7,175,834; 7,172,754; 7,175,835; 7,101,536; 7,078,022;5,175,340; 5,567,418, 5,538,716; 5,951,968; 5,670,140; 6,831,191;6,602,515; 7,166,273; 6,936,735; 6,699,463; 6,165,450; 7,150,876;6,962,692; 5,830,441.

Though a carrier by itself is sufficient, the sunscreen compositions maycontain various other components typically associated with skin careproducts. For example, various skin care agents including, but notlimited to, skin care excipients as well as additional photoprotectiveagents and skin lightening agents may be present. Such agents include,but are not limited to antioxidants, vitamins, anti-inflammatory agents,self-tanning agents, moisturizers, emollients, humectants, and the like,and mixtures thereof, in their conventional amounts. Agents and additivematerials of interest include those described in U.S. Pat. No.7,078,022.

Suitable antioxidants include, but are not limited to, water-solubleantioxidants such as sulfhydryl compounds and their derivatives (e.g.,sodium metabisulfite and N-acetyl-cysteine), lipoic acid anddihydrolipoic acid, resveratrol, lactoferrin, and ascorbic acid andascorbic acid derivatives (e.g., ascorbyl palmitate, ascorbylpolypeptide and ascorbyl phosphate). Oil-soluble antioxidants suitablefor use in the compositions of this invention include, but are notlimited to, butylated hydroxytoluene, retinoids (e.g., retinol andretinyl palmitate), tocopherols (e.g., tocopherol acetate), sodiumtocopheryl phosphate, tocotrienols, alkylresorcinols, curcurmin and itsderivatives and ubiquinone. Natural extracts containing antioxidantssuitable for use in the compositions of this invention, include, but notlimited to, extracts containing flavonoids and isoflavonoids and theirderivatives (e.g., genistein and diadzein), extracts containingresveratrol and the like. Examples of such natural extracts includegrape seed, green tea, pine bark, Phyllanthus emblica and propolis.Other examples of antioxidants may, be found on pages 1612-13 of the ICIHandbook as well as in U.S. Pat. No. 6,124,268.

The sunscreen compositions of the present invention may also include oneor more vitamins and/or their derivatives. Vitamins and vitaminderivatives include, for example, vitamin A, vitamin A propionate,vitamin A palmitate, vitamin A acetate, retinol, vitamin B, thiaminechloride hydrochloride (vitamin B₁), riboflavin (vitamin B₂),nicotinamide, vitamin C and derivatives (for example ascorbyl palmitate,magnesium ascorbyl phosphate, ascorbyl acetate), vitamin D,ergocalciferol (vitamin D₂), vitamin E, DL-α-tocopherol, tocopherol Eacetate, tocopherol hydrogensuccinate, vitamin K₁, esculin (vitamin Pactive ingredient), thiamine (vitamin B₁), nicotinic acid (niacin),pyridoxine, pyridoxal, pyridoxamine, (vitamin B₆), pantothenic acid,biotin, folic acid and cobalamine (vitamin B₁₂). Preferred vitamins are,for example, vitamin A palmitate, vitamin C and derivatives thereof,DL-α-tocopherol, tocopherol E acetate, nicotinic acid, pantothenic acidand biotin.

Suitable emollients include those agents known for softening the skinwhich may be selected from hydrocarbons, fatty acids, fatty alcohols,e.g., cetyl alcohol and stearyl alcohol, and esters. Petrolatum is acommon hydrocarbon type of emollient conditioning agent. Otherhydrocarbons that may be employed include alkyl benzoate, mineral oil,polyolefins such as polydecene, and paraffins, such as isohexadecane.Fatty acids and alcohols typically have from about 10 to 30 carbonatoms. Illustrative are myristic, isostearic, hydroxystearic, oleic,linoleic, ricinoleic, behenic and eruicie acids and alcohols. Oily esteremollients may be those selected from one or more of the following,triglyceride esters, acetoglyceride esters, ethoxylated glycerides, allesters of fatty acids, ether esters, polyhydric alcohol esters and waxesters. Additional emollients or hydrophobic agents include C₁₂ to C₁₅alkyl benzoate, dioctyladipate, octyl stearate, octyldodecanol, hexyllaurate, octyldodecyl neopentanoate, cyclomethicone, dicapryl ether,dimethicone, phenyl trimethicone, isopropyl myristate, capriylic/caprictriglycerides, siloxanes, e.g., cyclotetrasiloxane andcyclopentasiloxane, propylene glycol dicaprylate/dicaprate and decyloleate.

Suitable humectants include various polyhydric alcohols, especiallypolyalkylene glycols and, more preferably, alkylene polyols and theirderivatives. Exemplary humectants include propylene glycol, dipropyleneglycol, polypropylene glycol, polyethylene glycol, sorbitol,2-pyrrolidone-5-carboxylate, hydroxypropyl sorbitol, hexylene glycol,ethoxydiglycol 1,3-butylene glycol, 1,2,6-hexanetriol; glycerin,ethoxylated glycerin, propoxylated glycerin, compatible solutes, such asectoin, hydroxectoin, taurines, carnithine, acetyl carnithine andmixtures thereof. Also of interest are urea; guanidine; glycolic acidand glycolate salts (e.g. ammonium and quaternary alkyl ammonium);lactic acid and lactate salts (e.g. sodium, ammonium, and quaternaryalkyl ammonium); aloe vera in any of its variety of forms (e.g., aloevera gel); pyrrolidone carboxylic acids and their salts (e.g., sodiumpyrrolidone carboxylic acid); sugars and starches; sugars and starchesand their derivatives (e.g., honey extract, alkoxylated glucose);6-(N-acetylamino)-4-oxahexyltrimonium chloride; hyaluronic acid; chitin,lactamide monoethanolamine; acetamide monoethanolamine; propoxylatedglycerol; etc. In some instances, humectants of interest include, butare not limited to: C₃-C₆ diols and triols, such as the C₃-C₆ diols andtriols selected from the group consisting of propylene glycol,1,3-dihydroxypropane, glycerin, urea; honey extract, butylene glycol,hexylene glycol, 1,4-dihydroxyhexane, 1,2,6-hexanetriol, and mixturesthereof. In some instances, the humectants are those selected from thegroup consisting of glycerin, urea, honey extract, butylene glycol,hexylene glycol, and mixtures thereof. When employed in effectiveamounts, generally from 1 to 30%, preferably from 2 to 20%, by weight ofthe sunscreen composition, these additives serve as skin moisturizers aswell as reduce scaling and stimulate the removal of built-up scale fromthe skin.

In some instances, the compositions include one or more skinconditioning agents, where skin conditioning agents of interest includeocclusive skin condition agents, emollient skin conditioning agents andmiscellaneous skin conditioning agents, as well as combinations thereof.

Occlusive skin conditioning agents of interest include, but are notlimited to: avena sativa (oat) kernel oil, behenyl isostearate,caprylic/capric triglyceride, caprylic/capric/myristic/stearictriglyceride, caprylyl methicone, caprylyl trimethicone, safflower seedoil, cetyl palmitate, cetyl stearate, coconut oil, dimethicone PEG-8olivate, emu oil, glycol distearate, hydrogenated avocado oil,hydrogenated rice bran oil, propylene glycol diistearate, sweet almondoil, jojoba oil, squalane, stearyl beewax, stearyl dimethicone, cocoaseed butter, wheat germ oil, vegetable oil, etc.

Also of interest as skin conditioning agents are emollients. Thecompositions may include one or more emollients, which typically act tosoften, soothe, and otherwise lubricate and/or moisturize the skin.Suitable emollients that can be incorporated into the compositionsinclude, but are not limited to: oils such as petrolatum based oils,petrolatum, vegetable based oils, mineral oils, natural or syntheticoils, alkyl dimethicones, alkyl methicones, alkyldimethicone copolyols,phenyl silicones, alkyl trimethylsilanes, dimethicone, dimethiconecrosspolymers, cyclomethicone, cyclotetrasiloxane, cyclopentasiloxane,lanolin and its derivatives, fatty esters, glycerol esters andderivatives, propylene glycol esters and derivatives, alkoxylatedcarboxylic acids, alkoxylated alcohols, fatty alcohols, and combinationsthereof. Suitable esters could include, but not be limited to, cetylpalmitate, stearyl palmitate, cetyl stearate, isopropyl laurate,isopropyl myristate, isopropyl palmitate, glyceryl caprylate andcombinations thereof. The fatty alcohols could include but not belimited to octyldodecanol, lauryl, myristyl, cetyl, stearyl, behenylalcohol, and combinations thereof. Ethers such as eucalyptol, ceterarylglucoside, dimethyl isosorbic polyglyceryl-3 cetyl ether, polyglyceryl-3decyltetradecanol, propylene glycol myristyl ether, and combinationsthereof can also suitably be used as emollients.

Also of interest are miscellaneous skin conditioning agents. Examples ofmiscellaneous skin conditioning agents of interest include, but are notlimited to: alanine, algae extract, allantoin, aloe vera extract,aluminum PCA, apricot kernel amino acids, arbutin, arginine, asorbicacid, bisabolol, biotin, caffeine, calcium ascorbate, calendula oil,carnitine, carnosine, lime oil, orange oil, grapefruit oil, cucumberextract, tumeric extract, carrot seed oil, dipalmitoyl glutathione,dipalmitoyl hydroxyproline, dipotassium glycyrrhizate, disodiumadenosine phosphate, disodium adenosine triphosphate, elastin; fennelextract, ginko biloba extract, beta-glucan, glutamine, glycolipids,glycerrhizic acid, histidine, hyaluronic acid, hydrogenated polydecene,hydrolyzed algae extract, hydrolyzed collagen, hydrolyzed DNA,hydrolyzed oat protein, kinetin, lactic acid, linoleic acid, lysine,magnesium ascorbate, niacin, oat amino acids, oligopeptide-5,oligopeptide-6, oligopeptide-10, palmitoyl oligopeptide, papain, peaextract, sweet almond oil, apple extract, retinyl palmitate,resveratrol, soluble collagen, etc.

In some instances, the compositions include an emulsifying agent.Emulsifying agents of interest include, but are not limited to, sorbitanesters, glyceryl esters, polyglyceryl esters, methyl glucose esters,sucrose esters, ethoxylated fatty alcohols, hydrogenated castor oilethoxylates, sorbitan ester ethoxylates, polymeric emulsifiers, siliconeemulsifiers, glyceryl monoesters, preferably glyceryl monoesters ofC₁₆-C₂₂ saturated, unsaturated and branched chain fatty acids such asglyceryl oleate, glyceryl monostearate, glyceryl monopalmitate, glycerylmonobehenate, and mixtures thereof; polyglyceryl esters of C₁₆-C₂₂saturated, unsaturated and branched chain fatty acids, such aspolyglyceryl-4 isostearate, polyglyceryl-3 oleate, diglycerolmonooleate, tetraglycerol monooleate and mixtures thereof; methylglucose esters, preferably methyl glucose esters of C₁₆-C₂₂ saturated,unsaturated and branched chain fatty acids such as methyl glucosedioleate, methyl glucose sesquiisostearate, and mixtures thereof;sucrose fatty acid esters, preferably sucrose esters of C₁₂-C₂₂saturated, unsaturated and branched chain fatty acids such as sucrosestearate, sucrose trilaurate, sucrose distearate, C₁₂-C₂₂ ethoxylatedfatty alcohols such as oleth-2, oleth-3, steareth-2, and mixturesthereof; hydrogenated castor oil ethoxylates such as PEG-7 hydrogenatedcastor oil; sorbitan ester ethoxylates such as PEG-40 sorbitanperoleate, polysorbate-80, and mixtures thereof; polymeric emulsifierssuch as ethoxylated dodecyl glycol copolymer; and silicone emulsifierssuch as laurylmethicone copolyol, cetyldimethicone, dimethiconecopolyol, and mixtures thereof. (e.g. apricot kernel oil PEG-6 esters,beeswax, behenoyl stearic acid, ceteareth-2, cetearyl glucoside, cetylalcohol, cetyl phosphate, glyceryl palmitate, glyceryl caprylate,glyceryl stearate, hydrogenated lecithin, hydrolyzed beeswax, isostearylglucoside, palmitic acid, palm kernel acid, glyceride, PEG-20 stearate,PEG-100 stearate, oleic acid, stearic acid, stearyl alcohol, stearylphosphate, sucrose cocoate, sucrose palmitate, sucrose stearate, TEAstearate, tocopheryl phosphate, wheat germ oil PEG-8 esters, xanthangum, corn oil), etc.

The compositions of the disclosure can also include natural fats andoils. As used herein, the term “natural fat or oil” is intended toinclude fats, oils, essential oils, essential fatty acids, non-essentialfatty acids, phospholipids, and combinations thereof. These natural fatsand oils can provide a source of essential and non-essential fatty acidsto those found in the skin's natural barrier. Suitable natural fats oroils can include citrus oil, olive oil, avocado oil, apricot oil,babassu oil, borage oil, camellia oil, canola oil, castor oil, coconutoil, corn oil, cottonseed oil, emu oil, evening primrose oil,hydrogenated cottonseed oil, hydrogenated palm kernel oil, jojoba oil,maleated soybean oil, meadowfoam oil, palm kernel oil, peanut oil,rapeseed oil, grapeseed oil, safflower oil, sphingolipids, sweet almondoil, tall oil, lauric acid, palmitic acid, stearic acid, linoleic acid,stearyl alcohol, lauryl alcohol, myristyl alcohol, behenyl alcohol, rosehip oil, calendula oil, chamomile oil, eucalyptus oil, juniper oil,sandlewood oil, tea tree oil, sunflower oil, soybean oil, andcombinations thereof. The composition of the invention may include fatsand oils in an amount of from about 0.01% (by weight of the composition)to about 40% (by weight of the composition), such as from about 0.05%(by weight of the composition) to about 25% (by weight of thecomposition), and including from about 0.1% (by weight of thecomposition) to about 10% (by weight of the composition).

Suitable preservatives for use in the formulation of the presentinvention include, but are not limited to, one or more ofphenoxyethanol, ethylhexylglycerin; caprylyl glycol, sorbic acid, sodiumhydroxymethylglycinate, disodium salt of ethylenediaminetetraaceticacid, chloroxylenol, sodium benzoate, DMDM Hydantoin,3-iodo-2-propylbutyl carbamate, potassium sorbate, chlorhexidinedigluconate, the alkyl esters of para-hydroxybenzoic acid (the parabens,e.g. butylparaben, methylparaben and propylparaben), loniceracaprifolium (honeysuckle) flower extract & lonicera japonica(honeysuckle) flower extract.

Examples of anti-inflammatory ingredients include, but are not limitedto, bisabolol, curcurmin and its derivatives, retinoids, flavonoids andother polyphenolics etc. These and other anti-inflammatory agents, aswell as additional anti-oxidants and the like, are disclosed—US2005/0048008A1.

Examples of self-tanning ingredients include, but are not limited to,dihydroxyacetone and erythrulose.

The sunscreen compositions of the present invention may also include oneor more skin penetrants. These are additives that, when applied to theskin, have a direct effect on the permeability of the skin barrier:increasing the speed with which and/or the amount by which certain othercompounds are able to penetrate into the skin layers. Exemplary organicpenetration enhancers include dimethyl sulfoxide; isopropyl myristate;decyl, undecyl or dodecyl alcohol; propylene glycol; polyethyleneglycol, C₉₋₁₁, C₁₂₋₁₃ or C₁₂₋₁₅ fatty alcohols; none; alkylpyrrolidones; lecithin; etc. Surfactants can also be used as penetrationenhancers.

Other optional adjunct ingredients for the sunscreen compositions of thepresent invention include preservatives, waterproofing agents,fragrances, anti-foam agents, plant extracts (Aloe vera, witch hazel,cucumber, etc), opacifiers, stabilizers, skin conditioning agentscolorants, and the like, each in amounts effective to accomplish theirrespective functions.

The carrier may also contain other physiologically acceptable excipientsor other minor additives, particularly associated with organolepticproperties, such as fragrances, dyes, buffers, cooling agents (e.g.menthol), stabilizers or the like. The excipients and minor additiveswill be present in conventional amounts, e.g., ranging from about 0.001%to 5%, such as 0.001-2%, by weight, and in some instances not exceedinga total of 10% by weight.

Loaded Calcium Phosphate Particles

Where desired, the calcium phosphate particles may be loaded with anamount of one or more of the above components, e.g., anti-oxidants, UVabsorbers/blockers, etc. In such applications, loading protocolsdescribed in co-pending application Ser. No. 12/565,687 (the disclosureof which is herein incorporated by reference), may be employed.

Emulsion Formulations

As indicated above, in some instances the sunscreen compositions areemulsions, e.g., wherein the emulsion may be oil-in-water orwater-in-oil emulsion compositions. Of interest are oil-in-wateremulsified sunscreen compositions that include by weight:

(a) from 0.001% to 10% of Uniform Rigid Spherical Nanoporous CalciumPhosphate Particles as an ultra violet (UV) blocking and scatteringagent, e.g., as described above;

(b) from about 0.1% to about 50% of inorganic sunscreen component (e.g.,UV shielding particles) such as described above;

(c) from about 0.1% to about 15% of organic sunscreen component (e.g.,UV absorbers) such as described above;

(d) from about 0.1% to about 10% of solid wax or polymer film former forthe water proof function;

(e) 30% or more of the entire composition of a lipophilic component(e.g., made up of fats, oils, other lipophilic ingredients, etc.), e.g.,as described above;

(f) from 30 to 80%, such as 40 to 50% water.

In some instances, the above formulation includes one or more of thefollowing additional components:

(g) From about 0.01% to about 10% of Skin ConditioningAgent—Miscellaneous: Ex: Botanivera 1-200C (INCI: Aloe barbadensis LeafJuice);

(h) One or more viscosity enhancers (e.g Xanthan Gum) in an amount offrom about 0.01% (by weight of the composition) to about 25% (by weightof the composition), such as from about 0.05% (by weight of thecomposition) to about 10% (by weight of the composition), and includingfrom about 0.1% (by weight of the composition) to about 5% (by weight ofthe composition);

(i) From about 0.5% to about 25% of Humectant: e.g., Glycerin;

(j) From about 0.5% to about 20% of Skin Conditioning Agent—Occlusive:e.g., (INCI: Caprylic/Capric Triglyceride); Caprylyl Trimethicone;

(k) From about 0.01% to about 20% of Emulsifier and emulsion stabilizer:e.g. Lipomulse 165 (INCI: Glyceryl Stearate & PEG-100 Stearate); Capmul708 G (Glyceryl Caprylate); Cetyl Alcohol; Stearyl Alcohol;

(l) From about 0.5% to about 25% of Skin Conditioning agent—Emollient:e.g., Capmul 708 G (Glyceryl Caprylate); Botanisil CM-70(Cyclotetrasiloxane and Cyclopentasiloxane); Botanisil GB-20 (INCI:Cyclopentasiloxane & Dimethicone/Vinyl Dimethicone Crosspolymer;

(m) From about 0.5% to about 5% of Skin Conditioning Agent ViscosityIncreasing agent—nonaqueous: e.g., Botanisil GB-20 (INCI:Cyclopentasiloxane & Dimethicone/Vinyl Dimethicone Crosspolymer);

(n) From about 0.5% to 1.1% of Preservative: e.g., Euxyl PE 9010 (INCI:Phenoxyethanol & Ethylhexylglycerin);

(o) From about 0.001% to about 10% of Antioxidant; Skin ConditioningAgent—Miscellaneous; e.g., Sodium Tocopheryl Phosphate; TocopherylAcetate

(p) From about 0.01% to about 10% of Skin ConditioningAgent—Miscellaneous; Viscosity Increasing Agent—Aqueous; e.g.,Hyaluronic Acid

Container

In some instances, the sunscreen composition is present in container.The container may be configured to hold a desired amount of sunscreenand provide for storage stability of the sunscreen. In some instances,the container is configured to contain from 0.5 to 100 oz of sunscreencomposition, such as 1 to 50 oz of sunscreen composition.

As such, aspects of the invention include a container delimiting atleast one compartment, the container being closed by means of a closingmember; and a composition as described above and placed inside saidcompartment. The container may be in any appropriate form. It may inparticular be in the form of a bottle, a tube, a jar, a case, a box, asachet or a carton. The closing member may be in the form of a removablestopper, a lid, a cap, a tear-off strip or a capsule, in particular ofthe type comprising a body attached to the container and a cover caparticulated on the body. It may also be in the form of a member forselectively closing the container, in particular a pump, a valve or aflap valve. The product may be contained directly in the container, orindirectly. By way of example, the product may be arranged on animpregnated carrier, in particular in the form of a wipe or of a pad,and arranged (individually or in plurality) in a box or in a sachet.Such a carrier incorporating the product is described, for example, inWO 01/03538. The closing member may be coupled to the container byscrewing. Alternatively, the coupling between the closing member and thecontainer is done other than by screwing, in particular via a bayonetmechanism, by click-fastening, gripping, welding, bonding or by magneticattraction. The term “click-fastening” is in particular intended to meanany system involving the crossing of a bead or cord of material byelastic deformation of a portion, in particular of the closing member,followed by return to the elastically unconstrained position of saidportion after the crossing of the bead or cord. The container may be atleast partially made of thermoplastic material. By way of examples ofthermoplastic materials, mention may be made of polypropylene orpolyethylene. Alternatively, the container is made of non-thermoplasticmaterial, in particular of glass or of metal (or alloy). The containermay have rigid walls or deformable walls, in particular in the form of atube or of a tubular bottle. The container may comprise means fordistributing or facilitating the distribution of the composition. By wayof example, the container may have deformable walls so as to cause thecomposition to exit in response to a positive pressure inside thecontainer, this positive pressure being caused by elastic (ornon-elastic) squeezing of the walls of the container.

Fabrication Methods

Aspects of the invention further include methods of making the sunscreenformulations that include the uniform, rigid, spherical, nanoporouscalcium phosphate particles and topical compositions that include thesame. With respect to methods of making the formulations, aspects ofthese methods include combining an amount of uniform, rigid, spherical,nanoporous calcium phosphate particles comprising a porous structurethat defines an internal space; and a desired sunscreen deliveryvehicle.

Utility and Methods

The sunscreen compositions of the invention find use in a variety ofdifferent application, including sunblocking applications. Thecompositions are effective in reducing or preventing skin damage due toUV exposure, such as exposure to the sun. As such, aspects of theinvention include methods of protecting skin from damage due to UVexposure, where the methods include the step of applying sunscreencompositions according to embodiments of the invention to skin. In someinstances, the present invention provides a method of reducing orpreventing erythema resulting from exposure to UV light. Methods of theinvention may include applying the sunscreen composition to areas of theskin that are or may be exposed to the sun. In some instances, thesunscreen composition is applied to areas that are not typically exposedto the sun but that nevertheless have exposure to the penetrating UVrays. For example, tee shirts and other light fabrics offer minimalprotection against sun exposure, especially to UV rays. Thus, in someinstances the sunscreen compositions may be applied to essentially allareas of the body, including those typically covered by clothing.

The amount of the sunscreen composition that is to be applied to theskin may vary, so long as it is sufficient to provide the desired sunprotection. To some extent, the amount depends upon the form of thesunscreen composition and its mode of application. For example, a sprayformulation may be applied so as to provide a light, even coat on theskin. Lotions, creams, gels and the like may be applied at a rate ofabout 1 to 2 ounces for the entire body, i.e., for the exposed skin of a“average individual” wearing a swimsuit and standing 5 feet 4 inchestall, weighing 150 pounds, and having a 32 inch waist. This translatesto an application rate of about 2 mg/cm² of skin. On the face, anapplication rate of interest is ¼ to ⅓ of a teaspoon. In some instances,the application rate will be from about 0.1 to about 10 mg/cm²,preferably from about 1 to about 3 mg/cm², of skin.

In certain embodiments, the sunscreen composition is applied before sunexposure, such as at least 15 minutes before, and reapplied every 2hours or more frequently, e.g., if the individual engages inactivities/actions that may cause the sunscreen composition to wear orwipe off, e.g., swimming; washing dishes, windows, etc., washing handsand/or face; contact sports activities; activities that promotesubstantial sweating; etc.

In addition to the above-mentioned photo-protective benefits of thesunscreen compositions, the continual, e.g., daily, use of the sunscreencompositions of the present invention, regardless of whether oneanticipates UV exposure or not, provides in some instances a number ofadditional benefits to skin. For example, the continual use of thesesunscreen compositions may delay the appearance of fine lines, enhanceextracellular matrix cohesion, reduce the appearance of spider veins,improving skin firmness and elasticity: skin effects that are not only aresult of exposure to the sun but also the natural aging process. Forexample, the long-term use of the inventive sunscreen compositions mayhelp with thickening the keratinous tissue (i.e., building the epidermisand/or dermis layers of the skin), thereby preventing and/or retardingatrophy of human skin; preventing and/or retarding the appearance ofspider veins and/or red blotchiness on human skin; preventing and/orretarding the appearance of dark circles under the eye; preventingand/or retarding sallowness and/or sagging of human skin; soften and/orsmooth lips; preventing and/or relieving itch of human skin, regulatingskin texture (e.g. wrinkles and fine lines), improving skin color (e.g.redness, freckles); and the like.

The following examples are offered by way of illustration and not by wayof limitation.

EXPERIMENTAL I. Formulations

The following formulas were prepared. Formula 10090 lacks calciumphosphate particles and formulation 10091 includes an amount of calciumphosphate particles.

Raw Material % w/w Function LSC.RNB010091 Purified Water 47.325% SkinConditioning Agent - Miscellaneous; Solvent Botanivera 1-200C 0.100%Skin Conditioning Agent - Miscellaneous (INCI: Aloe barbadensis LeafJuice) Xanthan Gum 0.400% Viscosity Increasing Agent -Aqueous; Binder;Emulsion stabilizer Glycerin 8.000% Humectant Neo Heliopan ® 303 (INCI:6.000% Sunscreen agent Octocrylene) Ethylhexyl Salicylate 1.600%Sunscreen agent TiO2 (INCI: Titanium 1.750% Sunscreen agent Dioxide)Zinc Oxide 6.000% Sunscreen agent CCT (INCI: Caprylic/Capric 7.000% SkinConditioning Agent - Occlusive Triglyceride) Lipomulse 165 (INCI: 2.500%Emulsifier and emulsion stabilizer Glyceryl Stearate & PEG-100 Stearate)Capmul 708 G (INCI: 3.000% Skin Conditioning agent - Emollient: GlycerylCaprylate) Surfactant - Emulsifying agent Cetyl Alcohol 2.000% Emulsionstabilizer; Opacifying Agent; Surfactant Emulsifying Agent StearylAlcohol 2.000% Emulsion stabilizer; Opacifying Agent; SurfactantEmulsifying Agent Botanisil CM-70 5.000% Skin Conditioning Agent -Emollient (INCI: Cyclotetraxsiloxane and Cyclopentasiloxane) BotanisilGB-20 2.000% Skin Conditioning Agent - Emollient & (INCI:Cyclopentasiloxane & Viscosity Increasing agent - nonaqueousDimethicone/Vinyl Dimethicone Crosspolymer) Caprylyl Trimethicone 3.000%Skin Conditioning Agent - Occlusive Euxyl PE 9010 1.100% Preservative(INCI: Phenoxyethanol & Ethylhexylglycerin) Tocopheryl Acetate 0.100%Antioxidant; Skin Conditioning Agent - Miscellaneous Hyauronic Acid0.120% Skin Conditioning Agent - Miscellaneous; Viscosity IncreasingAgent -Aqueous Sodium Tocopheryl 0.005% Antioxidant; Skin ConditioningAgent - Phosphate Miscellaneous Hydroxysomes ™ calcium 1.000% Sunscreenphosphate particles (Laboratory Skin Care) LSC.RNB010090 Purified Water48.325% Skin Conditioning Agent - Miscellaneous; Solvent Botanivera1-200C 0.100% Skin Conditioning Agent - Miscellaneous (INCI: Aloebarbadensis Leaf Juice) Xanthan Gum 0.400% Viscosity Increasing Agent-Aqueous; Binder; Emulsion stabilizer Glycerin 8.000% Humectant NeoHeliopan ® 303 (INCI: 6.000% Sunscreen agent Octocrylene) EthylhexylSalicylate 1.600% Sunscreen agent TiO2 (INCI: Titanium 1.750% Sunscreenagent Dioxide) Zinc Oxide 6.000% Sunscreen agent CCT (INCI:Caprylic/Capric 7.000% Skin Conditioning Agent - Occlusive Triglyceride)Lipomulse 165 (INCI: 2.500% Emulsifier and emulsion stabilizer GlycerylStearate & PEG- 100 Stearate) Capmul 708 G (INCI: 3.000% SkinConditioning agent - Emollient: Glyceryl Caprylate) Surfactant -Emulsifying agent Cetyl Alcohol 2.000% Emulsion stabilizer; OpacifyingAgent; Surfactant Emulsifying Agent Stearyl Alcohol 2.000% Emulsionstabilizer; Opacifying Agent; Surfactant Emulsifying Agent BotanisilCM-70 5.000% Skin Conditioning Agent - Emollient (INCI:Cyclotetraxsiloxane and Cyclopentasiloxane) Botanisil GB-20 2.000% SkinConditioning Agent - Emollient & Viscosity (INCI: Cyclopentasiloxane &Increasing agent - nonaqueous Dimethicone/Vinyl DimethiconeCrosspolymer) Caprylyl Trimethicone 3.000% Skin Conditioning Agent -Occlusive Euxyl PE 9010 1.100% Preservative (INCI: Phenoxyethanol &Ethylhexylglycerin) Sodium Tocopheryl 0.005% Antioxidant; SkinConditioning Agent - Phosphate Miscellaneous Tocopheryl Acetate 0.100%Antioxidant; Skin Conditioning Agent - Miscellaneous Hyauronic Acid0.120% Skin Conditioning Agent - Miscellaneous; Viscosity IncreasingAgent -Aqueous

II. Procedure

The following procedure was employed to prepare the above formulations:

Phase A

Add the required amount of Purified Water of Phase A into a clean,sanitized vessel. Add the required amount of Botanivera 1-200 C, XanthanGum and Glycerin. Start heating of Phase A to 65° C.-70° C. and mix withpropeller-type mixing. Mix until dissolve and uniform. Hold temperaturefor phase combination.

Phase B

Prepare Phase B by combining into a suitably-sized clean and sanitizedvessel, Neo Heliopan 303, Ethylhexyl Salicylate, Caprylic/CapricTriglyceride, Lipomulse 165, Capmul 708G, Cetyl Alcohol, StearylAlcohol, Botanisil CM-70, Botanisil GB-20, Caprylyl Trimethicone. Heatto 65° C.-70° C. with mixing until melted and uniform. Add ZnO powderand TiO2 powder. Homogenized until uniform.

Phase Combination

When both phases are at 65° C.-70° C., start adding Phase B into Phase Ain the main batching vessel. Homogenize to achieve a very fine emulsion.

When the batch is free of air, commence cooling to 40° C. withpropeller-type mixing. Add the required amounts of Euxyl PE 9010,Tocopheryl Acetate, Hyaluronic Acid, Sodium Tocopheryl Phosphate. Mixuntil uniform.

For formula 10091, in a separate vessel at R.T. add Purified Water (PartII), sodium Tocopheryl Phosphate. Mix until Sodium Tocopheryl Phosphateis dissolved. Add Hydroxysomes™ and mix for 30 minutes. Add D to C.Homogenize until uniform.

III. Testing

Formulations 10090 and 10091 were tested by Helioscreen (Marseilles,France) for SPF and UV-A blocking ability, according to the followingprotocols.

A. SPF

The method employed is based on the protocol initially described in B.L. Diffey and J. Robson (J.S.C.C. 40, 127-133 May/June 1989) modifiedand improved to evaluate the skin protection against UVB. The methodconsists of evaluating the Sun Protection Factor (SPF) which expressesthe protection level a sun protection product brings through the full UVspectrum, using an adequate substrate on which the product has beenspread, by means of a spectrophotometric method. The employed methodconsists in measuring the flow of UV energy through a test product(transmitted energy) and in comparing this flow to the initial flowaccording to the spectrophotometric method:

T(λ)=I/I ₀, with λ as the wavelength.

The wave function represented by this ratio is not sufficient to expressthe level of protection of the spread on the skin product as it alsodepends on two others wavelength functions:

-   -   Spectral irradiance of the “Standard Sun” as defined by        “Commission Internationale de l'Eclairage”, wave function noted        S(λ).    -   Erythemal action spectrum which expresses the relationship        between cutaneous or subcutaneous reactions and energy of        excitation light, wave function noted E(λ).        S(λ) and E(λ) are known and tabulated values.

A “KONTRON 930” spectrophotometer equipped with an UV source and adouble monochromator able to deliver a flow of energy between 250 and800 nm was used. A 10⁻⁴ g precision laboratory balance to controldeposited product weight was employed, where the products were depositedwith a spatula. The following PMMA plates were used: HELIOPLATE® HD6guaranteed roughness, from HelioScreen® Labs. as substrate.

Deposition of the test sample was performed as small lined up spots allover the surface of the substrate. As deposited on the substrate,product quantity was checked by weighing. Application rate wasdetermined in such a way that the actual quantity of product left on thesubstrate before equilibration was 1.2 mg/cm². The application area wasgreater than 16 cm², in fact about 25 cm². A PMMA plate containing UVfilter was used as a reference so as to check the equipment was in goodworking order and to assess the relevance of carried out measures.

The in vitro SPF was expressed from the whole residual UVB and UVAspectrum having crossed the spread composition on substrate productlayer. This led to a wave function T(λ) which was multiplied by:

-   -   A first wave function S(λ), spectral irradiance of the Standard        Sun.    -   A second wave function E(λ), erythemal action spectrum.        The SPF was calculated from the ratio:

${{In}\mspace{14mu} {vitro}\mspace{14mu} {SPF}} = \frac{\int_{290\mspace{11mu} n\; m}^{400\mspace{11mu} n\; m}{{E(\lambda)} \cdot {S(\lambda)} \cdot {\lambda}}}{\int_{290\mspace{11mu} {nm}}^{400\mspace{11mu} {nm}}{{E(\lambda)} \cdot {S(\lambda)} \cdot {T(\lambda)} \cdot {\lambda}}}$

The SPF of the tested product was obtained by the calculation of thearithmetical average of the different measures: all measurescorresponding to selected samples were taken into account for thecalculation of the statistical dispersion.

B. UVA

The determination of the UVA protection factor or UVAPF was made using aspectrophotometric method as initially described by B. L. Diffey and J.Robson “A new substrate to measure sunscreen protection factorsthroughout the ultraviolet spectrum”, J. Soc. Cosmet. Chem., 40, 127-133(1989) for the SPF determination, then modified and adapted by Colipa(as reported athttp://www.colipa.com/site/index.cfm?SID=15588&OBJ=26783&back=1, n° 20)to evaluate the skin protection against UVA irradiation.

The employed method consisted of evaluating the protection brought by asun protection product within the UVA range, by means of aspectrophotometric method, using an adequate substrate on which theproduct has been spread. The test was based on the assessment of UVtransmittance through a thin film of the sun product sample, spread on aroughened substrate, before and after exposure to a controlled dose ofUV radiation, from a defined UV source. Due to the possible lack ofinter-laboratory reproducibility of in vitro SPF protection factormeasurement, this SPF value was adjusted to the lapelled in vivo SPFthrough the use of a multiplying coefficient C. The sunscreen sample wasexposed to an irradiation dose proportional to the initial UVAprotection factor (UVAPF0), calculated from the adjusted absorbance dataof the non exposed sample. The final in vitro UVA protection factor(UVAPF) is calculated from the adjusted absorbance data of the UVexposed sample.

The method used consisted of measuring the flow of UV energy through theproduct, expressed in transmitted energy and in comparing this flow tothe initial flow according to the principle of any spectrophotometricmethod:

T(λ)=I/I ₀, with λ as the wavelength.

Absorbance at wavelength λ is related to Transmittance by:

A(λ)=−log(T(λ)

Absorbance values were then multiplied by different irradiances andaction spectrums so as to be correlated to biological responses of invivo methods:For the SPF calculation:

-   -   By the source irradiance. This is the spectral irradiance of the        UV source I(λ).    -   And by the action spectrum related to the skin. This is the        Erythema action spectrum which expresses the relationship        between cutaneous or subcutaneous reactions and energy of        excitation light E(λ) (as defined by “Commission Internationale        de l'Eclairage”).        For the UVAPF calculation:    -   By the source irradiance. This is the spectral irradiance of the        UV source I(λ).    -   And by the action spectrum related to the skin. This is the        persistent pigment darkening    -   (PPD) action spectrum which expresses the relationship between        cutaneous or    -   subcutaneous reactions and energy of excitation UV light P(λ).    -   I(λ), E(( ) and P(( ) are known and tabulated values.        The determination of the UVAPF was made through the following        steps:    -   Step 1: In vitro measurement of absorbance A₀(λ) through the        spread on PMMA plate product prior to any UV irradiation.    -   Step 2: Mathematical adjustment of the initial UV spectrum using        coefficient ‘C’ to achieve an in vitro SPF (0% UV dose) equal to        the labeled (in vivo) SPF. Then initial UVA protection (UVAPF₀)        is calculated using A₀(λ) and C.    -   Step 3: A single UV dose D is calculated, proportional to        UVAPF₀. (D=UVAPF₀×1.2)    -   Step 4: UV exposure of the sample to the calculated UV dose D.    -   Step 5: In vitro transmission measurement of the sun product        after UV exposure. Acquisition of second UV spectrum with A(λ)        data.    -   Step 6: Mathematical adjustment of the second spectrum        (following UV exposure) according to the same C coefficient        previously determined in step 2, then calculation of the in        vitro UVA protection factor UVAPF.

A “KONTRON 930” spectrophotometer equipped with an UV source and adouble monochromator able to deliver a flow of energy between 250 and800 nm was employed. A single spot area about 1.2 cm² was evaluated. A10⁻⁴ g precision laboratory balance was employed to control depositedproduct weight. A spatula or syringe was employed deposit the product. AUV source for pre-irradiation: a CPS+SUNTEST (ATLAS) with standard andSchott WG320 filters were used. In this appliance the temperatureregulation of the samples was maintained in the 20° C.-40° C. range. Thefollowing PMMA plates have been used: HELIOPLATE® HD2 guaranteedroughness, from HelioScreen® Labs. as substrate.

Deposition of the test sample was performed as small lined up spots allover the surface. As deposited on the substrate, the sample quantity waschecked by weighing. Application rate was determined in such a way thatthe actual quantity of product left on the substrate beforeequilibration was 1.2 mg/cm². The application area was greater than 16cm², in fact about 25 cm².

The spectral irradiance at the exposure plane of the artificial UVsource that was used for radiation was as similar as possible to theirradiance at ground level under a standard zenith sun, as defined byCOLIPA (1994) or in DIN 67501 (1999). The UV irradiance was within thefollowing acceptance limits (measured at sample distance).

Light source specifications Total UV irradiance_((290 to 400 nm)) 50-140W/m² Irradiance ratio of UVA_((320 to 400 nm)) to UVB_((290 to 320 nm))8-22The reference standard sun has a total irradiance of 51.4 to 63.7 W/m²(Colipa 1994/DIN67501) and a UVA to UVB irradiance ratio of 16.9 to17.5. The device had the ability to maintain samples below 40° C. byusing air conditioning. The sample was exposed to full spectrum UVradiation but the dose is being defined by the UVA content.

For the pre-irradiation dose calculation, the Mean UVAPF₀ value foundwas 2.97 and was calculated as shown below. The single UVA applied dosewas calculated to be 4 (j/cm²) according to the formula:

D=UVAPF₀ ×D ₀ in J/cm²

D₀ being fixed at 1.2 J/cm² UVA (in j/cm²).

A PMMA plate containing UV filter was used as a reference so as to checkthe equipment was in good working order and to assess the relevance ofcarried out measures.

The in vitro SPF was calculated using the following formula:

${SPF}_{{in}\mspace{11mu} {vitro}} = \frac{\int_{\lambda = {290\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{E(\lambda)}*{I(\lambda)}*{\lambda}}}{\int_{\lambda = {290\mspace{11mu} {nm}}}^{\lambda = {400{nm}}}{{E(\lambda)}*{I(\lambda)}*10^{- {A_{0}{(\lambda)}}}*{\lambda}}}$

where:E(λ)=see aboveI(λ)=see aboveA₀(λ)=mean monochromatic absorbance of the test product layer before UVexposuredλ=wavelength step (1 nm)

Calculation of the adjusted in vitro SPF and determination of thecoefficient of adjustment C′:

C is the coefficient of adjustment, iteratively determined to adjust thecalculated in vitro SPF value to the labeled (in vivo) SPF value. It isrecommended that C falls within a range between 0.8 and 1.2.

$\begin{matrix}{{SPF}_{{{in}\mspace{11mu} {vitro}},{ad}_{j}} = {{SPF}{\mspace{14mu} \;}{labelled}}} \\{= \frac{\int_{\lambda = {290\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{E(\lambda)}*{I(\lambda)}*{\lambda}}}{\int_{\lambda = {290\; {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{E(\lambda)}*{I(\lambda)}*10^{{- {\Lambda_{0}{(\lambda)}}}*C}*{\lambda}}}}\end{matrix}$

The mean value of SPF in vivo was previously evaluated at: 11.70Therefore, the value of the (C) coefficient was calculated at: 1.00

UVAPF₀ is calculated for each plate individually, according to formula:

${UVAPF}_{0} = \frac{\int_{\lambda = {320\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{P(\lambda)}*{I(\lambda)}*{\lambda}}}{\int_{\lambda = {320\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{P(\lambda)}*{I(\lambda)}*10^{{- {\Lambda_{0}{(\lambda)}}}*C}*{\lambda}}}$

-   -   where: P(λ)=see above        Calculation of UVAPF of plates after UV irradiation of the        sample        The in vitro UVAPF was calculated using the following formula:

${UVAPF} = \frac{\int_{\lambda = {320\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{P(\lambda)}*{I(\lambda)}*{\lambda}}}{\int_{\lambda = {320\mspace{11mu} {nm}}}^{\lambda = {400\mspace{11mu} {nm}}}{{P(\lambda)}*{I(\lambda)}*10^{{- {\Lambda {(\lambda)}}}*C}*{\lambda}}}$

Where:

A(λ) is the mean monochromatic absorbance of the test product layerafter UV exposure.

Mean UVAPF0 and UVAPF Calculation:

Each plate was measured at 3 different sites to ensure that a total areaof at least 2 cm² was measured. UVAPF₀ or UVAPF of one plate wascalculated from the mean absorbance value from the 3 individual spots.When coefficient of variation of absorbance between spots exceeded 50%,then the plate was rejected and a new plate prepared. UVAPF₀ or UVAPF ofthe product was the mean of the UVAPF₀ or UVAPF's of three individualplates. When the coefficient of variation between the UVAPF₀ or UVAPF'sof the individual plates exceeded 20%, then further plates have beenmeasured until the coefficient of variation requirement was reached.

All tests corresponding to selected samples were taken into account forthe calculation of the statistical dispersion.

C. CONCLUSION

UVA SPF With HAX 3-5 2.80 11.69 ± 2.40 Without HAX 3-5 2.50  9.48 ± 2.27

The above results demonstrate that inclusion of calcium phosphateparticles in sunscreen formulations increases both the UV-A protectionfactor and sun protection factor of sunscreen compositions.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

Accordingly, the preceding merely illustrates the principles of theinvention. It will be appreciated that those skilled in the art will beable to devise various arrangements which, although not explicitlydescribed or shown herein, embody the principles of the invention andare included within its spirit and scope. Furthermore, all examples andconditional language recited herein are principally intended to aid thereader in understanding the principles of the invention and the conceptscontributed by the inventors to furthering the art, and are to beconstrued as being without limitation to such specifically recitedexamples and conditions. Moreover, all statements herein recitingprinciples, aspects, and embodiments of the invention as well asspecific examples thereof, are intended to encompass both structural andfunctional equivalents thereof. Additionally, it is intended that suchequivalents include both currently known equivalents and equivalentsdeveloped in the future, i.e., any elements developed that perform thesame function, regardless of structure. The scope of the presentinvention, therefore, is not intended to be limited to the exemplaryembodiments shown and described herein. Rather, the scope and spirit ofpresent invention is embodied by the appended claims.

What is claimed is:
 1. A sunscreen composition comprising: uniform,rigid, spherical, nanoporous calcium phosphate particles; and asunscreen delivery vehicle.
 2. The sunscreen composition according toclaim 1, wherein the uniform, rigid, spherical, nanoporous calciumphosphate particle is ceramic.
 3. The sunscreen composition according toclaim 1, wherein the uniform, rigid, spherical, nanoporous calciumphosphate particle has a diameter ranging from 0.05 to 50 μm.
 4. Thesunscreen composition according to claim 1, wherein the uniform, rigid,spherical, nanoporous calcium phosphate particle have a surface arearanging from 10 m²/g to 150 m²/g.
 5. The sunscreen composition accordingto claim 1, wherein the uniform, rigid, spherical, nanoporous calciumphosphate particle comprises pores are sintered.
 6. The sunscreencomposition according to claim 1, wherein the uniform, rigid, spherical,nanoporous calcium phosphate particle comprises pores are loaded withanti-oxidants.
 7. The sunscreen composition according to claim 1,wherein the uniform, rigid, spherical, nanoporous calcium phosphateparticle comprises pores are loaded with additional sunscreens.
 8. Thesunscreen composition according to claim 1, wherein the sunscreendelivery vehicle is an oil-in-water or water-in-oil emulsion.
 9. Thesunscreen composition according to claim 1, wherein the sunscreendelivery vehicle comprises inorganic UV shielding particles; organic UVabsorbers; a polymeric water-proof component and a lipophilic component.10. A sunscreen composition comprising by weight: (a) from 0.001% to 10%of uniform rigid spherical nanoporous calcium phosphate particles; (b)from about 0.1% to about 50% of inorganic UV shielding particles; (c)from about 0.1% to about 15% of organic UV absorbers; (d) from about0.1% to about 10% of a polymeric water-proof component; (e) 30% or morelipophilic component; and (f) water.
 11. The sunscreen compositionaccording to claim 10, wherein the uniform, rigid, spherical, nanoporouscalcium phosphate particle is ceramic.
 12. The sunscreen compositionaccording to claim 10, wherein the uniform, rigid, spherical, nanoporouscalcium phosphate particle has a diameter ranging from 0.05 to 50 μm.13. The sunscreen composition according to claim 10, wherein theuniform, rigid, spherical, nanoporous calcium phosphate particle have asurface area ranging from 10 m²/g to 150 m²/g.
 14. The sunscreencomposition according to claim 10, wherein the uniform, rigid,spherical, nanoporous calcium phosphate particle comprises pores aresintered.
 15. The sunscreen composition according to claim 10, whereinthe uniform, rigid, spherical, nanoporous calcium phosphate particlecomprises pores are loaded with anti-oxidants.
 16. The sunscreencomposition according to claim 10, wherein the uniform, rigid,spherical, nanoporous calcium phosphate particle comprises pores areloaded with organic or inorganic UV absorbers and/or blockers.
 17. Amethod comprising: applying a sunscreen composition comprising: (a)uniform, rigid, spherical, nanoporous calcium phosphate particles; and(b) a sunscreen delivery vehicle; to a topical region of a subject. 18.The method according to claim 17, wherein the topical region is akeratinized skin surface.